The proposed research program is designed to add to the fundamental understanding of carcinogenesis and thereby assist in developing specific approaches to the prevention of cancer as well as to chemotherapeutic methods of arresting cancer. Singlet oxygen has been found to be a potent oxidant of various biologically important substrates (amino acids, steroids, nucleic acids) to produce chemical carcinogens, mutagenically alter nucleic acids, and inactivate enzymes. Further, recent studies in our laboratories and others have demonstrated that this reactive species can be produced enzymatically, suggesting that the singlet oxygen may be significantly involved in inducing cancer in the body. We propose to investigate those several enzyme systems which we have predicted are biological sources of singlet oxygen, to study the mechanism of formation of 1O2, to research the reaction of enzymatically generated 1O2 with biologically important substrates that may be involved in carcinogenesis, and to develop anticancer agents based on the fundamental knowledge gained from these studies. Singlet oxygen has been previously implicated as an active agent in photochemically induced skin cancer. The proposed research on the enzymatic generation of singlet oxygen and the pathological damage caused by this species should allow the development of a more general understanding of carcinogenesis. More importantly, we believe that clinical programs for the prevention and control of various forms of cancer will be materially aided by this study.